Effects of seirogan (wood creosote) on propulsive colonic motility and stool characteristics in ambulatory mini-pigs.

Our goal was to determine whether Seirogan, an herbal medicine used as an antidiarrheal agent, modifies colonic function, including motility. Experiments were performed on four female Yucatan mini-pigs with established permanent cecal fistulas providing direct access to the colon. Long-term recordings of proximal colonic motility were accomplished by a solid-state probe (six pressure ports 10 cm apart), and a motility index was calculated. Stool viscosity was also measured. The laxative bisacodyl (15 mg/kg) was used to induce colonic motility (increase in motility index) and stool softening, prior to investigating the effect of Seirogan (2-15 mg/kg per os twice a day) or a vehicle control. Seirogan (15 mg/kg), but not the placebo, reversed the bisacodyl-induced stool softening and restored the motility index to normal values by reducing the number of propagating contractions. Taken together the results suggest that inhibition of proximal colonic motility by Seirogan may contribute to its antidiarrheal action.

Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats.

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Anti-diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro.

BACKGROUND: Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti-diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown. AIM: To examine the effect of seirogan on electrogenic ion transport in vitro. METHODS: Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh). RESULTS: Serosal or mucosal application of seirogan (0.1-100 microg/mL) decreased basal jejunal transmural PD. Pre-treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan-induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh-induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD. CONCLUSION: The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh-induced electrical responses, may contribute to its anti-diarrhoeal action.

[The study of Chinese herbal medicinal prescription with enzyme inhibitory activity. VI. The study of makyo-kanseki-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase].

A Chinese herbal medicinal prescription, Makyo-kanseki-to, was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The effect for the inhibitory activity of cAMP phosphodiesterase by combination with constituent crude drugs of the prescription was studied. Gypsum acted as a mitigatory component for Ephedra herb and Glycyrrhiza in cAMP phosphodiesterase inhibition test.

Inhibition of adenosine 3',5'-cyclic monophosphate phosphodiesterase by flavonoids from licorice roots and 4-arylcoumarins.

Isoliquiritigenin, glabridin, licoarylcoumarin and licoricidin were identified as strong inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase in waste materials which were obtained during the industrial extraction of glycyrrhizin from licorice roots. The structure-activity relationships of 12 flavonoids from licorice roots and 34 4-arylcoumarins were studied. In 4-arylcoumarins, 5,7-dihydroxy derivatives were generally highly inhibitory towards cAMP phosphodiesterase.

[The study of Chinese herbal medicinal prescription with enzyme inhibitory activity. IV. The study of the prescription containing mineral drug with adenosine 3',5'-cyclic monophosphate phosphodiesterase].

Twenty five Chinese herbal medicinal prescriptions containing gypsum, kaolin, longgu, oyster shell and sodium sulfate were studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate phosphodiesterase. The inhibitory activity of 15 prescriptions without mineral drug was higher than that of each original prescription. On the contrary, four were lower and six were not recognized to be different. All 11 prescriptions containing gypsum with an exception increased the inhibitory activity by removing gypsum. The half prescriptions containing kaolin or sodium sulfate also increased the inhibitory activity by removing the drug.

[The study on Chinese herbal medicinal prescription with enzyme inhibitory activity. II. The study of kanbaku-taiso-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase].

A Chinese herbal medicinal prescription, Kanbaku-taiso-to, was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The effect for the inhibitory activity of cAMP phosphodiesterase in combination with constituent crude drugs and difference in kind of crude drugs of the prescription were studied. The inhibitory activity of the prescriptions which were combined with low protein content wheat were higher than that with high protein content wheat.

[The study on Chinese herbal medicinal prescription with enzyme inhibitory activity. III. The study of mao-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase].

Mao-to, a Chinese herbal medicinal prescription was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The inhibitory activity for this enzyme depended mainly on Ephedra herb and Glycyrrhiza in this prescription. Apricot kennel acted as a mitigatory component for Ephedra herb in cAMP phosphodiesterase inhibitory test. In ephedrine and the related compounds the inhibitory activity of cAMP phosphodiesterase was not shown.